Med Hypotheses. 1979 Sep;5(9):969-85.
The nutritional regulation of T lymphocyte function.
Prostaglandin (PG) E1 plays a major role in the regulation of thymus development and T lymphocyte function and the evidence for this is reviewed. The production of PGE1 is dependent on nutritional factors with linoleic acid, gamma-linolenic acid, pyridoxine, zinc and vitamin C playing key roles.
Inadequate intake of any one of these will lead to inadequate PGE1 formation and defective T lymphocyte function.
Megadoses of any one are likely to be only minimally effective in the absence of adequate intakes of the others.
By careful attention to diet it should be possible to activate T lymphocyte function in the large number of diseases including rheumatoid arthritis, various auto-immune diseases, multiple sclerosis, and cancer in which such function is defective. It is possible that T lymphocytes may require both endogenous and exogenous PGE1 in order to function adequately. It is therefore of particular interest that many cancer cells and virally infected cells are unable to make PGE1 because they cannot convert linoleic acid to gamma-linolenic acid. The direct provision of gamma-linolenic or dihomo-gammalinolenic acids in these situations is worthy of full investigation.
Shye wrote:An "old fashioned" supplement for MS, which I've not seen mentioned on this site, is Evening Primrose Oil--which contains the omega 6 Gamma Linoleic Acid mentioned above (can't get this in other foods).
BACKGROUND: Research has focused mainly on the relationship of zinc and copper contents and physical stresses like running, cycling, etc. It has also been reported that other forms of stresses change the concentration of these trace elements in humans. However,there are no reports on the effects of high altitude induced hypoxic stress on the plasma levels of these metals. Since hypoxia is one of the important stresses, we considered it appropriate to observe the changes in the levels of zinc and copper concentrations and in certain related zinc and copper enzymes and hormones in the plasma of human volunteers on acute induction to high altitude. From these findings, we intended to ascertain whether supplementation of these trace elements would be required for optimal health under such conditions. HYPOTHESIS: On acute induction to hypoxia, contents of these trace elements may change as the requirements of stressed organs and tissue may increase. Hence, further supplementation may be beneficial under hypoxic stress for better adaptability. METHOD: Volunteers were divided into two groups: with and without zinc and copper salt supplementation. Blood samples were collected at sea level and on induction to acute hypoxia on days 3 and 10. Trace mineral contents and their related enzyme (alkaline phosphatase) and hormone (ceruloplasmin) levels were determined in plasma samples. RESULTS: Plasma zinc contents were significantly reduced upon induction to high altitude in the non-supplemented group, but not in the zinc-supplemented group. Alkaline phosphatase activity increased significantly upon induction to the high altitude stress. The enzyme activity remained elevated up to day 10 of the stress. Plasma copper contents and ceruloplasmin activity did not change upon induction to high altitude. CONCLUSION: Under hypoxic stress, circulating levels of zinc and alkaline phosphatase in plasma changed appreciably as plasma zinc was transported into the organs and tissues. However, circulating levels of copper and ceruloplasmin in plasma did not change, indicating no extra supplementation of copper is required under hypoxic stress.
American Journal of Clinical Nutrition, 1991 Vol 53, 403-412
Discovery of human zinc deficiency and studies in an experimental human model
The importance of zinc for human health was first documented in 1963. During the past 25 y, deficiency of zinc in humans due to nutritional factors and several disease states has now been recognized. The high phytate content of cereal proteins is known to decrease the availability of zinc, thus the prevalence of zinc deficiency is likely to be high in a population consuming large quantities of cereal proteins. Alcoholism, malabsorption, sickle cell anemia, chronic renal disease, and chronically debilitating diseases are now known to be predisposing factors for zinc deficiency. A spectrum of clinical manifestations ranging from mild to severe degree have now been recognized in human zinc-deficiency states. Zinc is required for many biological functions including DNA synthesis, cell division, and gene expression. It is required for the activity of many enzymes in biological systems. Recent studies indicate that zinc is needed for cell-mediated immunity.
The Journal of Infectious Diseases 2000;182:S62–S68
Effects of Zinc Deficiency on Th1 and Th2 Cytokine Shifts
Ananda S. Prasad
Nutritional deficiency of zinc is widespread throughout developing countries, and zinc‐deficient persons have increased susceptibility to a variety of pathogens. Zinc deficiency in an experimental human model caused an imbalance between Th1 and Th2 functions. Production of interferon‐γ and interleukin (IL)‐2 (products of Th1) were decreased, whereas production of IL‐4, IL‐6, and IL‐10 (products of Th2) were not affected during zinc deficiency. Zinc deficiency decreased natural killer cell lytic activity and percentage of precursors of cytolytic T cells. In HuT‐78, a Th0 cell line, zinc deficiency decreased gene expression of thymidine kinase, delayed cell cycle, and decreased cell growth. Gene expression of IL‐2 and IL‐2 receptors (both α and β) and binding of NF‐κB to DNA were decreased by zinc deficiency in HuT‐78. Decreased production of IL‐2 in zinc deficiency may be due to decreased activation of NF‐κB and subsequent decreased gene expression of IL‐2 and IL‐2 receptors.
Journal of the American College of Nutrition, Vol. 28, No. 3, 257-265 (2009)
Impact of the Discovery of Human Zinc Deficiency on Health
Ananda S. Prasad, MD, PhD, MACN
The essentiality of zinc was recognized 46 years ago. Zinc deficiency resulting in growth retardation, hypogonadism, immune dysfunction and cognitive impairment affects nearly 2 billion subjects in the developing world. High phytate content of the cereal proteins consumed in the developing world, results in decreased availability of zinc for absorption. Zinc therapy has been very successful and life saving measure in patients with acrodermatitis enteropathica and Wilson's disease. Beneficial therapeutic responses of zinc supplementation have been ovserved in acute diarrhea in children, chronic hepatitis C, shigellosis, leprosy, leishmaniasis, and common cold. Zinc supplementation was effective in decreasing incidences of infection in elderly and patients with sickle cell disease. Zinc supplementation was effective in preventing blindness in 25% of the elderly with dry type of age related macular degeneration. Zinc supplementation in the elderly decreased oxidative stress and decreased generation of inflammatory cytokines.
Zinc is an intracellular signaling molecule in monocytes, dendritic cells and macrophages and it plays an important role in cell-mediated immune functions and oxidative stress. Zinc is also an anti-inflammatory agent. These unique properties of zinc may have significant therapeutic benefits in several diseases in humans. In many diseases concurrent zinc deficiency may complicate the clinical features, affect adversely immunological status, increase oxidative stress and increase generation of inflammatory cytokines. Oxidative stress and chronic inflammation may play important causative roles in many chronic diseases, including atherosclerosis, several malignancies, neurological disorders, and auto-immune diseases. It is therefore, important that status of zinc is assessed and zinc deficiency corrected in these chronic diseases. A controlled clinical trial of zinc supplementation in these disorders in order to document the preventive and therapeutic effects of zinc is warranted.
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